The working hypothesis is that changes in the activities of brain mechanisms mediated by serotonin might underlie hallucinogenic, and perhaps psychotogenic reactions in man. The objectives are: 1) to characterize two models of serotonin receptor activity in rat brain, one behavioral, the other electrophysiological; 2) to use the models to study the extent of involvement of endogenous serotonin in the mode of action of hallucinogenic drugs. The results with a serotonin behavioral syndrome support the working hypothesis, i.e., a diverse group of tryptamine derivativs evoked behavioral signs of serotonin predominance. Pretreatments with amine synthesis inhibitors revealed that some hallucinogens require endogenous serotonin for their actions, while others are apparently direct receptor agonists. Further experimentation will include: 1) doses-response comparisons of a phenethylamine series in causing the syndrome; 2) studies of the effects of selected hallucinogens on an evoked response in the hippocampus of anesthetized rats. Research of these types should provide the information needed for rational approaches to the treatment of hallucinogen toxicity.